Purpose: :
To determine the safety profile of repeated doses of topicalMC-1101 in normal and early non-exudative (dry) age-relatedmacular degeneration (AMD) subjects. The effect of MC-1101 onsubjects’ choroidal blood flow (ChBF) was also investigated.

Methods: :
In this study, 31 subjects (11 AMD patients and 20 normals)aged 50 to 89 were treated contralaterally with MC-1101 andplacebo and dosed a total of 7 times over 3 days. A Nautilus1.0 VersiDoserTM (Mystic PharmaceuticalsTM) was used to instill30 microliters of study medication per dose. Safety assessmentsincluded vital signs, visual acuity, intraocular pressure, anterior/posteriorsegment slit-lamp examinations, and AE monitoring. Measurementsof ChBF were taken at baseline and at multiple post-drug instillationtime points using a compact, confocal laser Doppler flowmeter(Sion, Switzerland).

Results: :
MC-1101 was found to be safe and well tolerated; no significantsafety-related issues were reported. Mild and transitory ocularhyperemia was the most common treatment-related adverse event,which occurred in 21 (68%) MC-1101-treated eyes and 1 (3%) vehicle-treatedeye; however, this was expected given MC-1101’s mechanismof action. Results for ChBF found increased blood volume andvelocity values in MC-1101-treated eyes 2 hours after dosing,which returned to baseline 2 hours later. In the AMD group,modest increases in blood flow were found 30, 60 and 120 minutespost-dosing at Visit 1. Larger data variation found in AMD subjectssuggests that choroidal blood parameters may be more volatilein this group and/or that substantial technical difficultiesmake accurate choroidal blood flow measurement more difficultin this population.

Conclusions: :
Repeated dosing with MC-1101 was well-tolerated in both normaland AMD subjects. MC-1101 appears to play a role in the modulationof ChBF following topical administration. Since these resultsindicate that treatment with MC-1101 may affect choroidal physiology,potential benefits to subjects with dry AMD should be furtherexplored.